Trans-7-cis-9-dodecadien-1-yl acetate

ABSTRACT

1. A MIXTURE OF TRANS-7-CIS-9-DODECADIEN-1-YL ACETATE AND TRANS-7-TRANS-9-DODECADIEN-1-YL ACETATE,

United States Patent O cc Patented 223212:

3 845 108 TRANs-7-cls-9 miEcADIEN-LYL ACETATE Wendell I oellfzs, 652 W.N 0rth St.; Jan Kochansky, RD. 0

heatsstaettsat taa No Drawing. Filed Aug. 31, 1973, Ser. No. 393,360

Int. Cl. C07c 69/14 US. Cl. 260-488 H 2 Claims NaH/THFi CaH1.Pa.B1 (VI)oH0.cH=oH(oH2)5.o00oHi (V) ABSTRACT OF THE DISCLOSURE 10 l (c t) (t)Trans-7-cis-9-dodecadien-l-yl acetate has been syn- I thesized and foundto be a sex attractant for males of OHsCHzC 2)5 2 the species Lobesiabotrana (European grape vine moth), I a major pest of the vine. Methodsof preparing trans-7- i cis-9-dodecadien-1-yl acetate and a method ofutilizing (c t) (t) said compound as attracting agent are disclosed.O'HsCH2CIi=CHGH=OH(OH OH (VIII) FIELD OF THE INVENTION i Novel insectsex attractants. (c't) (t) RELATED APPLICATIONSCHa.CHz.CH=CHCH=CH.(CHM-0.0.011 None. (IX) -A male attracting compoundwhich is active towards DESCRIPTION OF THE PRIOR ART males of thespecies Lobesia botrana namely trans-7-cis-9- In recent years, theecological problems raised by the dodecadien-l-yl acetate has beensynthesized, and found widespread use of certain insecticides, inparticular haloactive in th in v tr and i V v t sts. genated aromaticssuch as DDT, have initiated the search The grape berry moth Lobesia(Polychrosis) botrana for more specific methods of destroying insectpests, is an extremely serious pest of the vine in Europe and which, ifthey do not entirely eliminate the use of such therefore the fi g of amale attractant compound for harmful insecticides as pesticides, atleast considerably cut this insect is of great utility in providingecologically dedown the area in which they are broadcast. One modesirable methods of reducing the population of this insect which has beenfound of great interest in recent years has without the necessity oflarge scale spraying which is been the use of sex attractants orpheromones to attract required at the present time. either the male orthe female of a particular species or DESCRIPTION OF THE PREFERRED anumber of species to a partlcular and small location EMBODIMENTS wherethey can be destroyed thereby interrupting the breeding cycle andcutting down the number of such pests A route is disclosed for thesynthesis of in the next season. One technique employed for thispurdodeeadieh-l'yl acetatepose is to isolate either the male or thefemale pheromone 40 111 the Preparation of -3' and insert it into aninsect trap which is then located in acetate a menoalkyl ester ofsuberie acid, suitably the area which it is desired to protect from aparticular the methyl ester is P p y esterifyihg suhelie species of mothor other insect. The vapor from the trap aeid With the pp p alkallol,Suitably lower alkahol attracts the inserts into the trap Where they areeither held s h s t a T ester 0) is converted to an y or killed, thusremoving them from the general populace. 5 7bfomoheptahoate, y aHuhsdleekel Ieaetloh, or, p

Two problems have been associated with this approach. ably, y e aetioh0f hromil'le h the P e of red The first problem is that of availability.Enormous nummefehfle OXlde 1n the absence of hght- The aetloh of allbers of laboratory reared inserts are required to produce appropriateoxidizing agent in the presence of a mild base the naturally occurringattractant. This clearly is not a upon the alkyl 7-bromoheptanoate (II),suitably pyridinecommercially feasible approach and therefore the natureN-oxide in the presence of sodium bicarbonate yields the of attractantsmust be determined and such compounds corresponding alkyl7-oxoheptanoate (III).

prepared synthetically. Compound (III) is then treated withdiethyl-Z-(cyclo;

hexylamino) ethane phosphonate (IV). Compound IV SUMMARY OF THEINVENTION is prepared by the method of Nagata and I-Iayase (J.Br.OH2.CH(OEt)-2 Chem. Soc., 1969, 460) utilizing diethyl formylmethanephosphonate, prepared by the method of Dawson and I Burger [IACS, 74,5312 (1952)], as starting material.

0 The iminophosphonate (IV) and the ester (III) are T reacted in thepresence of sodium hydride in tetrahydro )2 z )2 a t) 2 furan to yieldthe alkyl 9-oxooct-7-enoate (V). Reaction of propyltriphenylphosphoniumbromide (VI) (prepared i ICHSOH H from propylbromide andtriphenylphosphine) with the alkyl 9-oxooct-7-enoate (V) followed bysaponification i yields trans-7-cis, trans-9-dodecadienoic acid (VII).The (EtO)2P.CH CH0 H02C(OH2)7C 2 (I) acid (V1) is then reduced to thecorresponding alcohol l s Y m 014 (VIII), suitably by means of anorganometallic reducing NH (no fight) agent such as lithium aluminumhydride or sodium di- S a BKCHMC 020m hydro-bis-(Z-methoxy ethoxy)aluminate (Red-Al), yielding trans-7-cis, trans-9-dodecadien-1-ol (VIII)which is esterified to the desired trans-7-cis, trans-9-dodecadien- V iNaHC OHCEHNO l-yl acetate (IX) by treatment With an acetylating agent(1V) 11 such as acetic anhydride in pyridine.

Product (IX) is then purified by preparative gas liquid chromatographyto yield a mixture of trans-7-trans-9- dodecadienyl andtrans-7-cis-9dodecadienyl acetates containing at least 80% of the saidtrans/cis isomer. Since the trans/trans isomer has no substantialrepulsive or attractive effect, its presence in the mixture iscommercially acceptable.

The biological eificacy of the synthetic material was tested both byfield test and by electro-antennograms. The electro-antennograms wererun by a modification of the method and apparatus of Schnieder (FirstInt. Symp. on Olfaction and Taste, Oxford (1963), p. 85). In this test,antennae of the insect which had been prepared in the method describedby Schnieder and had been attached to an oscilloscope, were exposed toan air stream into which were injected 1 ml. puffs passing over a pieceof filter paper saturated with a small amount of the chemical materialunder test. The electrical responses of the antennae were measured onthe oscilloscope. The method is described in detail in British Pat. No.1,299,691 to Roelofs et al. Typical upwind orientation toward the odorsource observed with femal extracts were elicited by the syntheticchemical. Male orientation was still quantitive with 100 picograms.Quantitative excitation was elicited with pg., although there was littleorientation.

In the field tests, Sectar insect traps (3M Company) were charged withthe material under test and hung in fields where the moth was prevalent.

The attractant substance may be used per se. In order to obtain moreaccurate dispensing of the attractant it may be taken up in a suitablevolatile diluent. Any reaction inert volatile organic solvent may beemployed. Lower alkanols such as methanol or ethanol ethers, such asdiethyl ether, halogenated hydrocarbons such as methylene chloride andalkyl ketones such as acetone or the like may be employed.

These solvents will evaporate very rapidly leaving the attractant in thetrap which may then volatilize slowly.

The rate of volatilization may be reduced by dissolving the attractantin a substantially non-odorous reaction inert viscous liquid. The natureof this viscous liquid is not critical, however, olive oil has beenfound suitable as an attractant keeper as has glycerol trioctanoate,mineral oil and Nujol. The use of such keepers permits the raising ofdosage per trap to about 10,000 ,ug. This permits the traps to be activefor a longer time without creating the repulsant eflect noted with highconcentrations of sex attractants.

It will be seen therefore that the preparation of compositions of theattractant, a keeper, and a diluent is most desirable. The concentrationof the components is not critical as the determining factor is theamount dispensed per trap. Thus, where a 1 ml. sample comprising 10 mg.is to be dispensed per trap a suitable composition would be as follows:

Trans-7-cis-9-dodecadien-l-yl acetate g 10 Olive oil ml 100 Ethanol ml900 EXAMPLE I Mononiethyl ester of suberic acid (*I) 4 EXAMPLE 11Methyl-7-bromoheptanoate (II) Monomethyl suberate (55.8 g., 0.30 moles),red mercuric oxide (120 g., 0.55 moles), and carbon tetrachloride (1 l.)were mixed and heated to reflux. The reaction flask was wrapped toexclude light, and bromine (72 g., 0.45 moles) in carbon tetrachloride(350 ml.) was added slowly. The mixture was refluxed and stirred for 2hours, then filtered and evaporated. To remove residues of mercurysalts, the filtrate was extracted with several portions each ofdistilled water, dilute nitric acid, and again distilled water.Filtration of the organic layer through a pledget of anhydrous magnesiumsulfate and evaporation of filtrate produced a material of satisfactorypurity for the next reaction. IR, 1745 cmr GLC one major peak andseveral minor ones comprising a total of ca 5% of the mixture.

In accordance with the foregoing procedure but where, in place of methylsuberate, there is used ethyl, propyl or butyl suberate, there iscorrespondingly produced ethyl, propyl or butyl 7-bromoheptanoate.

EXAMPLE III Methyl-7-oxoheptanoate (III) Methyl 7-brornoheptanoate (23g., 103 moles), pyridine-N-oxide (20 g., 210 mmoles), sodium bicarbonate(18 g., 212 mmoles) and toluene (250 ml.) were mixed, heated to vapourtemperature of 110 to azeotrope out water, then refluxed under nitrogenfor 4 hours. The mixture was cooled and poured into iced water (500ml.). The organic layer was separated and the aqueous phase wasextracted twice with petroleum ether (3060). The combined organic layerswere evaporated and the residue was distilled to yield 18.5 g. ofproduct, containing ca 50% methyl 7-oxoheptanoate (III) by gas liquidchromatography. The product was reprocessed, treating it as startingmaterial to yield a substantially pure methyl 7-oxoheptanoate.

EXAMPLE IV Methyl 9-oxooct-7-enoate (V) Diethyl 2-(cyclohexylimino)ethane phosphonate (V) (6 g.) in tetrahydrofuran (75 ml.) is added to anice cooled suspension of sodium hydride in tetrahydrofurau under anatmosphere of nitrogen. The sodium hydride suspension is freshlyprepared by Washing a sodium hydride/mineral oil suspension (1.25 g.,57%) three times with tetrahydrofuran (25 ml.) and discarding the first2 washes thereby removing the mineral oil. The mixture is stirred for 15minutes. Methyl 7-oxoheptanoate (III) (4.2 g., 26 mmol) intetrahydrofuran (25 ml.) is added and the mixture stirred at 25 for 2hours. The reaction mixture is quenched by pouring into water andextracted with petroleum ether (Skellysolve B). The extracts are Washedwith saturated aqueous sodium chloride, the solvent removed underreduced pressure and the residue dissolved in benzene ml.). To thebenzene solution is added oxalic acid (400 ml., 1% aq.) and the mixturestirred at 25 for 48 hours in an nitrogen atmosphere. The benzene layeris separated and dried over magnesium sulfate. Evaporation of thesolvent yields methyl 9-oxooct- 7-enoate (V) which is used withoutpurification in the next step.

EXAMPLE V Propyltriphenylphosphonium bromide (VI) n-Propyl bromide (10.2g., 0.083 moles); triphenyl phosphine (23 g., 0.088 moles); and benzene(60 ml.) were mixed and refluxed under nitrogen overnight. The mixturewas cooled and filtered. The solids were washed on the filter withbenzene and diethyl ether, then dried under vacuum over phosphoruspentoxide, to yield propyltriphenyl phosphonium bromide (VI) (8.7 g.,27%) which was used without further purification. Further refluxing ofthe filtrate gave additional material.

(VI) (10.5 g.) prepared in accordance with Example V is added andstirred vigorously while the ammonia is evaporated. Evaporation iscontinued over approximately 4 hours, the last traces being removed byimmersion of flask in warm water. Benzene (150 ml.) is added and themixture refluxed for 30 minutes, and cooled. The benzene solution ofmethyl 9-oxooct-7-enoate (V) prepared in accordance with Example IV(supra) is then added over a period of 2 hours under a nitrogenatmosphere. Stirring is continued at 25 for a further hour. The reactionmixture is quenched by pouring into water and the solvent layer washedthoroughly with Water. The solvent is then removed under reducedpressure on a rotary evaporator and the residue saponified by heatingunder reflux with ethanolic potassium hydroxide (9:1, 50 ml.) for 2hours. The mixture is again quenched by pouring into water and extractedsequentially with petroleum ether (Skel1ysolve B) and benzene. Theorganic extracts are-discarded and the aqueous layer acidified withaqueous hydrochloric acid, and extracted with benzene. The benzeneextract is washed with water, dried over magnesium sulfate, and thesolvent removed under reduced pressure to yieldtrans-7-cis,trans-9-dodecanoic acid (VII) which is used without furtherwork-up in the next stage.

EXAMPLE VII Trans-7-cis,trans-9-dodecadien-1-ol (VIII) Red-Al (10 g., 35mmoles); being a 70% solution in benzene of sodiumdihydro-bis-(Z-methoxy ethoxy) aluminate, is placed in a flask undernitrogen. Trans-7- cis,trans-9-dodecadienoic acid (VII) (from exampleVI) in benzene (50 m1.) is added slowly. The mixture is heated underreflux for 1 hour, cooled, 10% sodium hydroxide (100 ml.) added dropwiseunder nitrogen and extracted three times with petroleum ether (30-60%).The combined extracts are washed with aqueous sodium chloride untilneutral, filtered through anhydrous magnesium sulfate and evaporated toyield crude trans-7-cis, trans-9-dodecadien-1-ol.

EXAMPLE VIII Trans-7-cis,trans-9-dodecadien-1-yl acetate (IX) The crudealcohol (VIII) produced in accordance with the previous example is takenup in a mixture of acidic anhydride in pyridine (10 ml.+10 ml.) andheated for 45 minutes on a steam bath. The crude reaction mixture isquenched by pouring into water and extracting with petroleum ether. Theorganic extract is then further washed successively with water, ice coldaqueous hydrochloric acid (10%), saturated aqueous sodium bicarbonate,and saturated aqueous sodium chloride. The extract is dried overmagnesium sulfate and the solvent removed under reduced pressure toyield trans-7-cis,trans- 9-dodecadien-1-ol acetate (IX) (1.8 g., 30%from III, about 70% pure).

The thus prepared crude trans-7-cis,trans 9-dodecadienl-yl aceatecontains undesirable low boiling fractions 6 which are removed bypreparative gas liquid chromatography (3% phenyl diethanolaminesuccinate (PDEAS) on 60/80 mesh Gas chrom Z at The product from thepreparative scale chromatography is sufliciently pure for attractantuse. Rechromatography on an analytical scale column (3% PDEAS) on100/120 chromosorb W, nitrogen at 40 m1./min. gave thetrans-7-cis-9-isomer at 8.75 mins. and the trans-7-trans 9 isomer in 9.7mins. (ratio 9:1).

IR (film) of trans-7-cis-9-dodecadien-1-yl acetate fraction (from GLC)shown A 3350, 2980, 2950, 2870, 1700, 1245, 990 and 956 CHLTI.

If (film) of trans'7-trans-9-dodecadien-l-yl acetate (from GLC) showed 12980, 2950, 2870, 1700, 1245, 996 cmf FIELD TESTS The tests were carriedout by placing measured amounts of attractant containing at least 80% byweight of the given amount of cis-9-trans-7-dodecadien-1-yl acetate inthe traps.

The results are summarized below.

TABLE 1 [L. botrana trapping with trans-7, cis-9-dodeeadien-l-yl acetateand virgin females] Mean number males] 1 Large polyethylene cap andrubber septum as described in Roelofs, et al., Envir. Ent. 2225B (1973).The small polyethylene cap is 10 mm. 1 m. 3vith an 8.5 mm. dia. capinserted as cover (Semadeni and (30.,

e111 tn lgaflS fpllowed by the same letter are not significantlydifferent at 8 Eve 3 Wild males trapped during first flight May 17-June3, 1973 at State. ZH; treatments replicated 4 times and sampled androtated 8 times.

Trapping of released laboratory-reared males May 28430, 1973 atWadenswil, treatments replicated 5 times.

6 Five virgin females.

What is claimed is:

1. A mixture of trans-7-cis-9-dodecadien-l-yl acetate andtrans-7-trans-9-dodecadien-1-yl acetate.

2. The compound trans-7-cis-9-dodecadien-l-yl acetate.

Chem. Abstracts, 77:110559m.

Chem. Abstracts, 76:4211lm.

Chem. Abstracts, 77:113750c. Chem. Abstracts, 41:7657b.

VIVIAN GARNER, Primary Examiner U.S. c1. X.R. 260-410.9 R, 413, 483,487, 632 R, 638 R; 424-84

1. A MIXTURE OF TRANS-7-CIS-9-DODECADIEN-1-YL ACETATE ANDTRANS-7-TRANS-9-DODECADIEN-1-YL ACETATE,